Protective Mechanism Of Ghrelin Via Lipid Metabolism Pathway In Chronic Intermittent Hypoxia-induced Arteriosclerosis In Rats

Objective:This study was to observe chronic intermittent hypoxia and aggravate the disorder of lipid metabolism,and then participate in the relevant mechanisms of the development of arteriosclerosis(AS),and determine the specific mechanism of Ghrelin's regulation of this process.Methods:Chronic intermittent hypoxic rat model was used to simulate the obstructive sleep apnea-hypopnea syndrome.The chronic hypoxia/reoxygenation pathophysiology that occurred during sleep was used to conduct corresponding experimental research.Twenty-four male Wistar rats were randomly divided into 3 groups of 8 in each group:control group,chronic intermittent hypoxia(CIH)group,chronic intermittent hypoxia +Ghrelin group(experimental group).Chronic intermittent hypoxic conditions:Rats were placed in intermittent hypoxia animal compartments to provide intermittent hypoxia(minimum inhaled oxygen concentration 5%,maximum inhaled oxygen concentration 20%-21%,each maintenance time 45 seconds,188 seconds once Circulation);Intermittent hypoxia stimulation total time:8 hours per day,7 days per week for 5 weeks for a total of 35 days.During the 5 weeks of model establishment,all three groups of rats were given a high-fat diet.and the experimental group was given an intraperitoneal injection of ghrelin 100 ?g/kg once daily.After 5 weeks,all rats survived.After the end of the experiment(day 36),the rats in the three groups were directly anesthetized and blood was collected from the heart.The blood was measured for blood lipids(TC,CHO,HDL,LDL)and C-reactive protein levels(CRP)were used to measure the thickness of injured arteries and the ratio of intima-media thickness in HE staining.The expression of RhoA,PPAR?,LXRa and ABCA1 protein was detected by Western blot.Results:Compared with the control group,the arterial intima of the hypoxic group was significantly thickened,serum triglyceride,cholesterol,LDL,and CRP were elevated,serum HDL was decreased,P<0.05;serum HDL was increased in the hypoxia+Ghrelin group compared with the hypoxic group.Serum triglycerides,cholesterol,LDL,CRP P<0.05.Western blot:RhoA hypoxia group was significantly elevated compared with the control group,and PPAR?/LXR?/ABCA1 was significantly decreased(p<0.05).The expression of RhoA was decreased and the expression of PPAR?/LXRa/ABCA1 was increased in hypoxia+Ghrelin group compared with hypoxia group(p<0.05).Conclusions:(1)chronic intermittent hypoxia is a new stressor of AS,which can induce the occurrence and development of AS;(2)in the chronic gap hypoxia,dyslipidemia expression may be the reason for its promotion of AS process;(3)Chronic interstitial hypoxia can aggravate the disorder of blood lipid metabolism through RhoA/PPAR?/LXRa/ABCA1 pathways,and provide new ideas for targeted treatment of AS;(4)ghrelin can reduce dyslipidemia and delay artery by positively regulating RhoA/PPARy/LXR/ABCA1 pathways.The hardening process is expected to become a new drug for intervention in AS.